Atropine eye drops

 
 

HOW IS ATROPINE USED FOR MYOPIA CONTROL?

Either atropine eye drops or ointment are placed on the eye, normally once a day. The treatment is continued as long as myopia progression is considered a risk.     

HOW DOES ATROPINE WORK FOR MYOPIA CONTROL?

Atropine has been found in several studies to reduce the progression of myopia, meaning that patients who were given the drug did not become as myopic as those patients without the medication. Different studies show different results. The Atropine for the Treatment of Myopia (ATOM) study using commercially available 1% Atropine eye drops once nightly showed nearly a complete halt to myopic changes over a two year period: .25 units of change vs 1.20 units for the "no-drug" group. Another study (Shih 2001) found that atropine combined with multifocal glasses (to allow the student to read) had less effect: .40 units of change vs 1.40 units of change for a "no-drug" group over 18 months. Kennedy (1995) found that the atropine group had essentially no change (.05 units/year) vs. the "no-drug" group (.36 units/year). Lois Tong reported that eyes progressed in myopia faster when atropine drops are stopped. Many other studies have been done. Here's a partial listing from pubmed about atropine and myopia prevention.

Atropine was presumed for many years to have its effect due to its action of stopping the eye's ability to change focus. This was due to its action on the ciliary muscle, the muscle that controls the eye's focus. The thought was that since people who read more often (not always) became more myopic, then maybe the action of the ciliary muscle was causing the myopic changes. The story turns out to be more complicated than that. One study showed that when variables are carefully controlled, reading by itself does not cause myopia (Jones 2007) but myopic parents and lack of outdoor time do cause more myopia. (You can read more about reading and myopia at this link from the website Myopia: Prevention and Control) Because it is thought that atropine does not control myopia by acting only on the ciliary muscle, but the choroid and sclera of the eye also respond to atropine, and are being investigated for their role. The short story is that we don't really know yet why atropine works as it does in the eye.  The newest theory is that atropine acts directly or indirectly on the retina or sclera inhibiting stretching or thinning of the sclera and thus inhibiting growth.  

WHAT IS ATROPINE?

Atropine is a molecule derived from different plants that will attach itself to what are called muscarinic receptors, specific structures found throughout the body as part of the parasympathetic nervous system.

The action gets a bit complicated. For instance, atropine affects the body by blocking acetylcholine from attaching to these same receptors. Acetylcholine makes the muscle work, atropine stops it from working. If you want a general outline of the sympathetic and parasympathetic nervous system, collectively called the autonomic nervous system, here is a link to a site (Merck): Autonomic Nervous System.

In the eye these muscarinic receptors can be found in two muscles (among other locations), the pupillary sphincter and the ciliary muscles and the result of atropine attaching is that the muscles can't function, becoming paralyzed until the drug wears off. Since the pupillary sphincter makes the pupil smaller and the ciliary muscle shifts the eye's focus back and forth between near and far objects, the result is an eye with a dilated pupil that can't change focus.

WHAT IS ATROPINE NORMALLY USED FOR IN THE EYE?

Atropine is a drug normally used in the eye to make the pupil bigger and to prevent the eye from being able to change focus. Doctors will say that it produces mydriasis and cycloplegia, which means the same thing. Atropine is useful to a doctor because dilation makes it possible to see more of the inside of the eye during an exam. The paralyzing of ability to change focus is useful as a treatment for some specific types of eye inflammations that cause pain due to the focusing muscle becoming inflamed. Atropine stops the muscle from working so it won't hurt so much. Atropine also helps in some other specific types of eye exams.

ARE THERE ANY SIDE EFFECTS?

Atropine at high doses can be fatal but the same can be said of aspirin. Dosage levels used in the eye are considered very safe from the standpoint of extreme reactions. Unusual reactions are possible for any drug.

A person who uses commercially available atropine 1% eye drops will generally be very sensitive to light due to pupil dilation, allowing approximately 20 times more light into the eye compared to an non-dilated pupil. Pupils will be large, so the patient will look "different", as if they are "on-drugs", which they are. Sunglasses are necessary whenever outdoors.

The same person will also complain that they can't change focus between near and far. The focusing result will depend on their type of focusing system (nearsighted, farsighted, etc) and whether they are wearing their glasses or contact lenses for clear distance vision, but a common result is that when wearing glasses to see the board at school, a student would not be able to focus on or read the book on their desk.  Atropine normally wears off in a few days and so students after routine exams are generally told to wear sunglasses outdoors and to either take off their glasses to read (if nearsighted) or just avoid reading until things return to normal the next day or so. If the drops are used every day for myopia control, reading glasses, bifocals or removal of glasses (depending on the patients's spectacle prescription) will be necessary for any clear vision within arms's length, such as desk work or reading.

A few patients will develop red or irritated eyes.

Dr. Fenn recommends a concentration of atropine that is 1/100th the concentration of the commercially available atropine 1% solution.  Thus, very few of the aforementioned side effects are ever present.  In that Atropine for the Treatment of Myopia Study 2 (ATOM2) there was only one case of ocular irritation and one case of blur in 84 subjects in the 0.01% treatment group in the ATOM 2 Study.  There was one case of acute gastric pain requiring hospitalization in the 0.01% group not thought to be attributed to atropine.  Also, only 6% of patient requested glasses to help with bright light and for reading. 


ATROPINE IS NOT HEALTH CANADA OR FDA APPROVED FOR MYOPIA CONTROL

In Canada and the United States, atropine is not approved for myopia control but could be used "off-label", meaning that the doctor can decide to use an approved drug for a non-approved reason. The patient would probably need to be given what is called "informed consent", which generally means they have been told that the drug hasn't been studied as much for safety and effectiveness for the off-label use. Low dose daily aspirin for protection against heart problems is probably the most commonly cited example of an "off-label" use of a drug but there are many others.

PHARMACOLOGICAL FACTS OF ATROPINE 0.01% TREATEMENT FOR MYOPIA CONTROL

If topical atropine is the desired choice for patients and parents Dr. Fenn will after a thorough eye examination with measurement of blood pressure, pulse and intraocular pressure will prescribe 0.01% atropine (available at compounding pharmacies) of one drop per day to be administered at bedtime.  As the Atropine for the Treatment of Myopia Study 2 (ATOM 2) determined, the use of 0.01 % used once daily was very safe.  However, no medication or treatment comes without its adverse effects or complications.  In addition, the long term effects of atropine on children have not been studied.  However, it has been used for many years in children for the treatment of amblyopia (lazy eye).  I have listed the adverse ocular and systemic effects below in addition to discussing the risks and signs of  severe adverse reactions due to extremely toxic levels of atropine.

Ocular effects

  • Direct irritation from the drug itself
  • Generally the pupils dilate only 1 mm larger with the use of 0.01% atropine based on the Atropine for the Treatment of Myopia Study 2(ATOM 2). 
  • Decrease in accommodation or ability to focus for near objects.  The effects of 0.01% atropine used once a day had a minimal effect on accommodation.  Patients retained 11.3 diopters of accommodation according to the ATOM 2 study.  For perspective, to read a book at 40 cm you require only 2.50 diopters of accommodation.
  • Allergic contact dermatitis. 
    • Usually involves the eyelids and presents as redness, hives and swelling
    • Can involve the cornea and results in burning, light sensitivity and redness
    • No cases were present in the Atropine 0.01% group in the ATOM 2 Study.
  • Elevation of intraocular pressures.
    • More common in patients with a prior diagnosis of primary open angle glaucoma which is very rare in children
  • Risk of angle closure glaucoma. 
    • The risk is remote in patients without a previous history

Systemic Reactions to Atropine in Children 

  • Diffuse cutaneous flush
  • Depressed salivation/thirst
  • Fever
  • Urinary retention
  • Tachycardia (rapid heart rate) 
  • Somnolence (drowsiness) 
  • Excitement/restlessness and hallucinations
  • Speech disturbances
  • Ataxia (lack of coordination of voluntary muscle movements)

It must be noted that there was only one case of ocular irritation and one case of blur in 84 subjects in the 0.01% treatment group in the ATOM 2 study.  There was one case of acute gastric pain requiring hospitalization in the 0.01% group not thought to be attributed to atropine.

sEVERE ADVERSE EFFECTS DUE TO TOXIC LEVELS OF ATROPINE

A large portion of topically applied atropine rapidly enters the systemic circulation.  Adverse systemic reactions appear to be dose dependent, although patients vary in susceptibility.  Depression of salivation and drying of the mouth are usually the first signs of toxicity.  Slightly higher doses produce facial flushing and inhibit sweating.  Adverse systemic symptoms and central nervous system (CNS) manifestations generally occur at 20 times the minimum dose of 1%.  Effects are increased with the use of antihistamines, phenothiazines and tricyclic anti-depressants.  

Convulsions have been associated with topical ocular atropine instillation, particularly in children.  Deaths have been attributed to topical ocular atropine.  Six reported cases in the literature have occurred in children 3 years of age and younger.  The dosages applied ranged from 1.8 mg to 18 mg, but the cases were poorly documented.  Most of the children either were ill or had motor and mental retardation.  However, the cases imply that care must be taken not to overdose small children.  Caution should be also exercised particularly with children who have lightly pigmented eyes and individuals who have spastic paralysis or brain damage.  Two drops of 1% solution contain 1 mg of the drug.  In the concentrations used for myopia control, one drop of 0.01% solution once a day results in 0.005mg of the drug.  In order to get 1 mg of the drug equivalent to two drops of regular (1%) atropine you would have to take 200 drops of 0.01% atropine.  Caution should be exercised when storing atropine as with all medications to keep them in a safe place out of reach of small children.